Potential immunocompetence of proteolytic fragments produced by proteasomes before evolution of the vertebrate immune system

Niedermann, Gabriele; Grimm, Rudolf; Geier, E.; Maurer, Martina; Realini, Claudio; Eichmann, Klaus

doi:10.1016/s0165-2478(97)85760-4

Cited by 7 publications

(7 citation statements)

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“…All other molecules, such as calreticuliu, ER60 and calnexin, either are not absolutely required or their invertebrate homologs substitute for their function during MHC asssembly. Since antigen presentation in insect cells could be inhibited by the proteasome inhibitor lactacystin, it can be further concluded that the housekeeping proteasome is generally able to generate class I-binding peptides, in agreement with in vitro observations (30). Thus, although additional auxiliary molecules, such as interferon-induced proteasome subunits, might be required to generate some specific peptides or to optimize peptide prodtiction, these observations clearly define the minimal non-housekeeping molecules required for MHC class I antigen presentation.…”

Section: Tapasin Controls Mhc Class I Loading With Peptides In the Ersupporting

confidence: 83%

A comparison of viral immune escape strategies targeting the MHC class I assembly pathway

Früh¹,

Gruhler²,

Krishna³

et al. 1999

Immunological Reviews

105

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Peptide fragments from proteins of intracellular pathogens such as viruses are displayed at the cell surface by MHC class I molecules thus enabling surveillance by cytotoxic T cells. Peptides are produced in the cytosol by proteasomal degradation and translocated into the endoplasmic reticulum by the peptide transporter TAP. Empty MHC class I molecules associate with TAP prior to their acquisition of peptides, a process which is assisted and controlled by a series of chaperones. The first part of this review summarizes our current knowledge of this assembly pathway and describes recent observations that tapasin functions as an endoplasmic reticulum retention molecule for empty MHC class I molecules. To defeat the presentation of virus-derived peptides, several DNA viruses have devised strategies to interfere with MHC class I assembly. Although these evasion strategies have evolved independently and differ mechanistically they often target the same step in this pathway. We compare escape mechanisms of different viruses with particular emphasis on the retention of newly synthesized MHC class I molecules in the endoplasmic reticulum and the inhibition of peptide transport by viral proteins.

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Section: Tapasin Controls Mhc Class I Loading With Peptides In the Ersupporting

confidence: 83%

A comparison of viral immune escape strategies targeting the MHC class I assembly pathway

Früh¹,

Gruhler²,

Krishna³

et al. 1999

Immunological Reviews

105

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“…The observation that Ova8 presentation could be inhibited by lactacystin implicates the proteasome in the processing of ovalbumin in D.melanogaster cells, as observed in mammalian cells (Craiu et al, 1997). The ability of invertebrate proteasomes to generate the correct epitopes from precursor peptides has also been demonstrated in vitro (Niedermann et al, 1997). Taken together, these data support the hypothesis that the MHC class I system has taken advantage of the pre-existing ubiquitinproteasome system to display the by-products of protein turnover at the cell surface.…”

Section: Discussionmentioning

confidence: 85%

Retention of empty MHC class I molecules by tapasin is essential to reconstitute antigen presentation in invertebrate cells

et al. 1999

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Presentation of antigen-derived peptides by major histocompatibility complex (MHC) class I molecules is dependent on an endoplasmic reticulum (ER) resident glycoprotein, tapasin, which mediates their interaction with the transporter associated with antigen processing (TAP). Independently of TAP, tapasin was required for the presentation of peptides targeted to the ER by signal sequences in MHC class I-transfected insect cells. Tapasin increased MHC class I peptide loading by retaining empty but not peptide-containing MHC class I molecules in the ER. Upon co-expression of TAP, this retention/release function of tapasin was sufficient to reconstitute MHC class I antigen presentation in insect cells, thus defining the minimal non-housekeeping functions required for MHC class I antigen presentation.

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“…The MHC class I system appears to have evolved by adapting to the proteolytic fragments produced by proteasomes [36]. In turn, the proteasomal system has been optimized by evolving alternative proteolytically active b subunits whose expression depends on IFN-c, produced during immune responses.…”

Section: Discussionmentioning

confidence: 99%

Expression of housekeeping and immunoproteasome subunit genes is differentially regulated in positively and negatively selecting thymic stroma subsets

et al. 2004

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The expression of housekeeping and/or immunoproteasomes in isolated thymic stroma subsets has so far not been analyzed but may have important consequences for self peptide repertoires presented by MHC class I molecules during positive and negative thymic selection. Here we determined the expression of housekeeping and immunoproteasome b subunits and of PA28 in positively and negatively selecting stroma subsets. Positively selecting cortical thymic epithelial cells (cTEC) expressed only housekeeping but no immunoproteasome b subunit mRNA and proteins. However, immunoproteasome b subunits could be induced in cTEC by infection with Listeria monocytogenes or injection of IFN-c. In negatively selecting stroma including medullary epithelial cells and dendritic cells, incomplete and low representation of housekeeping b subunit proteins but high and complete expression of immunoproteasome b subunit proteins suggests absence of proper housekeeping proteasomes and predominance of immunoproteasomes. Expression of immunoproteasome b subunits in negatively selecting stroma was independent of IFN-c receptor as shown in knockout (KO) mice. Absence of LMP2 altered thymic selection of the MHC class I-restricted transgenic P14 TCR in KO mice. The data suggest that negative selection may primarily involve immunoproteasome peptide repertoires and that peripheral infection may influence peptide repertoires involved in positive selection.

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Potential immunocompetence of proteolytic fragments produced by proteasomes before evolution of the vertebrate immune system

Cited by 7 publications

References 0 publications

A comparison of viral immune escape strategies targeting the MHC class I assembly pathway

A comparison of viral immune escape strategies targeting the MHC class I assembly pathway

Retention of empty MHC class I molecules by tapasin is essential to reconstitute antigen presentation in invertebrate cells

Expression of housekeeping and immunoproteasome subunit genes is differentially regulated in positively and negatively selecting thymic stroma subsets

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